The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants

Journal article

Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta-infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor-binding domain (RBD). Two of these RBD-binding mAbs recognize a neutralizing epitope conserved between SARS-CoV-1 and -2, while 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y, including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses.

Authors: Liu, C; Zhou, D; Nutalai, R; Duyvesteyn, HME; Tuekprakhon, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: Cell Host & Microbe
• Volume: 30
• Issue: 1
• Pages: 53-68
• Article number: e12
• Place of publication: United States
• Publication date: 2021-11-27
• Acceptance date: 2021-11-22
• DOI: 10.1016/j.chom.2021.11.013
• EISSN: 1934-6069
• ISSN: 1931-3128
• Pmid: 34921776
• Language: English
• Keywords: FFR; structure; vaccine; antibody; immune responses; beta variant; spike protein; neutralization; receptor-binding domain; SARS-CoV-2; COVID-19